The cyclic AMP receptor protein modulates quorum sensing, motility and multiple genes that affect intestinal colonization in Vibrio cholerae
The cyclic AMP receptor protein modulates quorum sensing, motility and multiple genes that affect intestinal colonization in Vibrio cholerae
复制标题
DOI：
10.1099/mic.0.2007/006668-0
复制
发表时间：
2007-09-01
期刊：
影响因子：
2.8
通讯作者：
Benitez, Jorge A.
中科院分区：
文献类型：
--
作者：
Liang, Weili;Pascual-Montano, Alberto;Benitez, Jorge A.
霍乱弧菌是霍乱的病原体，在亚洲、非洲和拉丁美洲仍然是一个主要的公共卫生问题。这种细菌可以在人类宿主之外存活，并在浮游生物和生物膜群落生活方式之间交替存在。不同生活方式之间的转变是由包括群体感应在内的多种信号转导途径介导的。锌金属蛋白酶血凝素(HA)/蛋白酶的表达受群体感应调节因子HapR和cAMP受体蛋白的双重调控。在先前的研究中，我们观察到camp受体蛋白（CRP）的突变缺陷表达较低水平的HapR。为了进一步研究CRP在调节HapR和其他信号转导通路中的作用，我们对El Tor生物型霍乱弧菌的Delta CRP突变体进行了全球基因表达谱分析。本研究表明，CRP是霍乱自诱导剂1 （CAl-1）的生物合成所必需的，并影响多个hapr调节基因的表达。正如预期的那样，δ crp突变体产生了更多的霍乱毒素和增强的生物膜。鞭毛基因的表达，据报道在Delta hapR突变体中受到影响，在Delta crp突变体中减少。然而，上位分析表明，cAMP-CRP通过一种独立于HapR的机制影响运动性。据报道，crp的失活抑制了多种基因的表达，这些基因在体内被强烈诱导，并影响霍乱弧菌在小肠定植和致病的能力。这些基因包括编码外膜蛋白的ompU、ompT和ompW，肠道定植所需的替代sigma因子sigma(E)，以及参与厌氧能量代谢的基因。我们的研究结果表明，CRIP通过影响霍乱弧菌在人类宿主和环境中生存所需的群体感应和多个基因，在霍乱弧菌的生命周期中起着至关重要的作用。
Vibrio cholerae is the causative agent of cholera, which continues to be a major public health concern in Asia, Africa and Latin America. The bacterium can persist outside the human host and alternates between planktonic and biofilm community lifestyles. Transition between the different lifestyles is mediated by multiple signal transduction pathways including quorum sensing. Expression of the Zn-metalloprotease haemagglutinin (HA)/protease is subject to a dual regulation which involves the quorum-sensing regulator HapR and the cAMP receptor protein. In a previous study, we observed that a mutant defective in the cAMP-receptor protein (CRP) expressed lower levels of HapR. To further investigate the role of CRP in modulating HapR and other signal transduction pathways, we performed global gene expression profiling of a Delta crp mutant of El Tor biotype V. cholerae. Here we show that CRP is required for the biosynthesis of cholera autoinducer 1 (CAl-1) and affects the expression of multiple HapR-regulated genes. As expected, the Delta crp mutant produced more cholera toxin and enhanced biofilm. Expression of flagellar genes, reported to be affected in Delta hapR mutants, was diminished in the Delta crp mutant. However, an epistasis analysis indicated that cAMP-CRP affects motility by a mechanism independent of HapR. Inactivation of crp inhibited the expression of multiple genes reported to be strongly induced in vivo and to affect the ability of V. cholerae to colonize the small intestine and cause disease. These genes included ompU, ompT and ompW encoding outer-membrane proteins, the alternative sigma factor sigma(E) required for intestinal colonization, and genes involved in anaerobic energy metabolism. Our results indicate that CRIP plays a crucial role in the V. cholerae life cycle by affecting quorum sensing and multiple genes required for survival of V. cholerae in the human host and the environment.